On October 12, 2023 FORE Biotherapeutics reported the acceptance of an abstract on new nonclinical data related to plixorafenib (FORE8394), the company’s novel, investigational, small-molecule, next-generation, orally available selective inhibitor of BRAF alterations at the 2023 AACR (Free AACR Whitepaper)-NCI-EORTC International Conference, taking place October 11-14, 2023, in Boston and virtually (Press release, Fore Biotherapeutics, OCT 12, 2023, View Source [SID1234635916]). The data set presented in the poster shows improved drug activity for both V600 and non-V600 BRAF alternations from other pan-RAF and BRAF inhibitors.
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Poster
Abstract number: A095
Title: The paradox-breaker BRAF inhibitor plixorafenib (FORE8394) efficiently inhibits non-V600 mutations and fusions
Presentation Session Date/Time: Oct 12, 2023, 12:30-4 p.m. Poster Session
About plixorafenib (FORE8394)
Plixorafenib is an investigational, novel, small-molecule, next-generation, orally available selective inhibitor of mutated BRAF. It was designed to target a wide range of BRAF mutations while sparing wild-type forms of RAF. Preclinical studies and clinical trials have shown that its unique mechanism of action effectively inhibits not only the constitutively active BRAFV600 monomers targeted by first-generation RAF inhibitors but also disrupts constitutively active dimeric BRAF class 2 mutants, fusions, splice variants and others. Unlike first-generation RAF inhibitors, plixorafenib does not induce paradoxical activation of the RAF/MEK/ERK pathway. As a "paradox breaker," plixorafenib could therefore treat acquired resistance to current RAF inhibitors and, more generally, yield improved safety and more durable efficacy than first-generation RAF inhibitors. The company previously announced interim data from the ongoing Phase 1/2a clinical trial evaluating plixorafenib in patients with advanced solid tumors (including brain and spinal cord tumors) with activating BRAF alterations, providing evidence of durable anti-tumor activity in patients with BRAF-mutated cancers. The data were presented at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress (ESMO) (Free ESMO Whitepaper) in September 2022 and ASCO (Free ASCO Whitepaper) 2023.